Psilocybin Therapy for Depression in Parkinson's Disease

(PDP2 Trial)

Overseen By Joshua Woolley, MD,PhD

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Joshua Woolley, MD, PhD

Must not be taking: Psilocybin interactions

Disqualifiers: Psychosis, Cognitive impairment, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Prior Safety Data This treatment has passed at least one previous human trial

Approved in 2 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 2

60 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores whether psilocybin, a psychedelic compound, can ease depression symptoms in people with Parkinson's Disease. Participants will receive either a low or high dose of psilocybin in a safe, monitored environment, with support sessions before and after. It suits those diagnosed with Parkinson's who experience depression and can attend sessions at UCSF. The goal is to determine if this treatment can improve both mood and quality of life. As a Phase 2 trial, the research focuses on measuring the treatment's effectiveness in an initial, smaller group of people.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop your current medications, but it excludes those who regularly use medications that might interact with psilocybin. It's best to discuss your specific medications with the study team.

Is there any evidence suggesting that psilocybin therapy is likely to be safe for humans?

Research shows that psilocybin is usually safe in clinical settings. In past studies, participants mostly experienced mild and short-lived side effects, such as nausea and slight changes in mood or perception. Serious side effects are rare. Psilocybin has been researched for its potential to treat various conditions. Although not yet approved by the FDA, its use in controlled environments has proven generally safe. Participants in these studies typically receive doses under supervision, effectively managing any possible side effects. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Most treatments for depression in Parkinson's disease focus on balancing neurotransmitters like dopamine or using antidepressants. But psilocybin works differently by targeting serotonin receptors, which may lead to rapid changes in mood and perception. Researchers are excited because psilocybin could offer improvements in mood and emotional well-being with just a few doses, potentially providing faster and more lasting relief than traditional therapies. This psychedelic compound is administered in a controlled setting, which helps ensure both safety and support for participants during their experience.

What evidence suggests that psilocybin might be an effective treatment for depression in Parkinson's Disease?

Research has shown that psilocybin may help treat depression. In studies, participants reported significant improvement and fewer depression symptoms after psilocybin therapy. This trial will include two separate psilocybin administration sessions, where participants will receive one dose of psilocybin, ranging from low ("microdose") to high, in a monitored setting. This treatment affects serotonin, a brain chemical that influences mood and emotions, potentially reducing feelings of sadness and hopelessness. Although data specifically for Parkinson's patients is limited, the general antidepressant effects appear promising. Early findings suggest that psilocybin could also benefit those with depression related to Parkinson's Disease. ^{1 2 3 4 5}

Who Is on the Research Team?

Joshua D Woolley, MD, PhD

Principal Investigator

University of California, San Francisco

Ellen Bradley, MD

Principal Investigator

University of California, San Francisco

Are You a Good Fit for This Trial?

This trial is for English-speaking adults aged 40-80 with Parkinson's Disease (stages 1-3) and depression, who can attend visits at UCSF. They must have a doctor managing their condition but cannot join if they have psychotic symptoms, significant cognitive issues, or use certain medications like dopamine agonists or MAO inhibitors.

Inclusion Criteria

Comfortable speaking and writing in English

Able to attend all in-person visits at UCSF as well as virtual visits

I have Parkinson's diagnosed by a neurologist, in early to mid-stage.

Exclusion Criteria

Psychotic symptoms involving loss of insight

I have significant memory or thinking problems.

A health condition that makes this study unsafe or unfeasible, determined by study physicians

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Preparation and Integration

Participants undergo psychotherapy sessions before and after each psilocybin administration session

4-6 weeks

Multiple visits (in-person)

Psilocybin Administration Session 1

Participants receive one dose of psilocybin in a monitored setting with preparation and integration sessions

1 day

1 visit (in-person)

Psilocybin Administration Session 2

Participants receive a second dose of psilocybin in a monitored setting with preparation and integration sessions

1 day

1 visit (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

12 weeks

Multiple visits (in-person and virtual)

What Are the Treatments Tested in This Trial?

Interventions

• Psilocybin

Trial Overview The study aims to see if psilocybin therapy helps improve depressive symptoms in those with Parkinson's Disease. Participants will receive psilocybin treatment and their symptom changes will be monitored.

How Is the Trial Designed?

Group I: Psilocybin Administration Session 2 Experimental Treatment 1 Intervention

Participants will receive one dose of psilocybin ranging from low ("microdose") to high in a monitored setting with preparation sessions before and integration sessions after.

Group II: Psilocybin Administration Session 1 Experimental Treatment 1 Intervention

Participants will receive one dose of psilocybin ranging from low ("microdose") to high in a monitored setting with preparation sessions before and integration sessions after.

Psilocybin is already approved in United States, European Union for the following indications:

Approved in United States as Psilocybin for:

• Treatment-resistant depression (TRD) under Breakthrough Therapy designation

Approved in European Union as Psilocybin for:

• Treatment-resistant depression (TRD) under PRIME designation

Who Is Running the Clinical Trial?

Joshua Woolley, MD, PhD

Lead Sponsor

Trials

3

Recruited

100+

Published Research Related to This Trial

Psilocybin has shown significant therapeutic effects in reducing symptoms of depression and anxiety in patients with life-threatening diseases, based on a systematic review and meta-analysis of clinical trials involving 92 patients.

The results indicate that psilocybin may be a safe and effective treatment option, particularly for cases resistant to conventional therapies, with significant improvements measured by the Beck Depression Inventory and State-Trait Anxiety Inventory.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Psilocybin as a New Approach to Treat Depression and Anxiety in the Context of Life-Threatening Diseases-A Systematic Review and Meta-Analysis of Clinical Trials. Vargas, AS., Luís, Â., Barroso, M., et al.[2020]

In a study of 27 patients with moderate to severe major depressive disorder, psilocybin-assisted treatment showed significant and lasting antidepressant effects, with 75% of participants experiencing a treatment response and 58% achieving remission after 12 months.

There were no serious adverse events related to psilocybin, indicating a favorable safety profile, and participants reported meaningful personal and spiritual experiences that correlated with increased well-being, although these did not directly predict improvements in depression.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and safety of psilocybin-assisted treatment for major depressive disorder: Prospective 12-month follow-up. Gukasyan, N., Davis, AK., Barrett, FS., et al.[2022]

In a study involving 12 healthy adults, escalating doses of psilocybin (0.3, 0.45, and 0.6 mg/kg) were administered safely, with no serious adverse events reported, indicating a favorable safety profile for this psychedelic compound.

The pharmacokinetics of psilocin, the active metabolite of psilocybin, were linear across the tested doses, with an elimination half-life of about 3 hours, suggesting that no dose adjustments are necessary for individuals with mild to moderate renal impairment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pharmacokinetics of Escalating Doses of Oral Psilocybin in Healthy Adults. Brown, RT., Nicholas, CR., Cozzi, NV., et al.[2022]

A single, moderate dose of psilocybin significantly reduced depressive symptoms in 52 participants with major depressive disorder, showing a decrease of 13.0 points on the MADRS scale compared to baseline, which was significantly greater than the placebo group.

54% of participants in the psilocybin group met the criteria for remission of depression 14 days after treatment, and no serious adverse events were reported, indicating a favorable safety profile for this novel treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Single-dose psilocybin-assisted therapy in major depressive disorder: A placebo-controlled, double-blind, randomised clinical trial. von Rotz, R., Schindowski, EM., Jungwirth, J., et al.[2023]

A single dose of psilocybin (0.5-20 mg/kg) significantly increases the expression of genes related to neuroplasticity in the prefrontal cortex and hippocampus, suggesting its potential therapeutic effects for mental health disorders.

The study highlights that psilocybin's effects on gene expression are dose-dependent and predominantly observed in the prefrontal cortex, emphasizing the need to assess both gene expression and protein translation to understand its rapid effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Transcriptional regulation in the rat prefrontal cortex and hippocampus after a single administration of psilocybin. Jefsen, OH., Elfving, B., Wegener, G., et al.[2022]

Psilocybin has shown promise in clinical trials for reducing symptoms of depression, indicating its potential as a novel treatment option.

Patients with treatment-resistant depression (TRD) may benefit the most from psilocybin therapy, although the risks associated with its use are still not fully understood.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Assessing potential of psilocybin for depressive disorders. Kozak, Z., Johnson, MW., Aaronson, ST.[2023]

Psilocybin, a hallucinogenic compound found in certain mushrooms, has been associated with increasing rates of drug abuse, highlighting the need for comprehensive pharmacological understanding.

Despite its historical use in the 1960s for experimental medical purposes, recent research has only begun to uncover the pharmacological properties of psilocybin, indicating a gap in knowledge that needs to be addressed.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The pharmacology of psilocybin. Passie, T., Seifert, J., Schneider, U., et al.[2016]

Psilocybin, derived from Psilocybe cubensis mushrooms, is being investigated as a novel treatment for major depression, with a focus on its safety and efficacy compared to traditional antidepressants.

The proposed study will include both preclinical toxicity evaluations in mice and a clinical trial assessing the safety and pharmacokinetics of psilocybin in healthy adults, followed by an open trial in patients with major depressive disorder, aiming to provide comprehensive data on its therapeutic potential.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A Proposal to Study the Safety and Efficacy of Psilocybe cubensis in Preclinical and Clinical Studies as a Therapeutic Alternative for Major Depressive Disorder. Escamilla, R., González-Trujano, ME., González Mariscal, JM., et al.[2023]

Psilocybin, a serotonergic psychedelic, has shown promise in treating various psychiatric disorders, including depression and substance use disorders, with 9 clinical trials conducted between 2000 and 2020.

The treatment is generally well tolerated with limited side effects, and some patients with treatment-resistant conditions have experienced significant long-term improvements after just a few sessions, indicating its potential efficacy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Treatment with psilocybin: applications for patients with psychiatric disorders]. Breeksema, JJ., Koolen, MHB., Somers, M., et al.[2021]

Psilocybin-containing mushrooms, commonly known as hallucinogenic or 'magic' mushrooms, rapidly affect the central nervous system within 0.5-1 hour of ingestion, leading to effects such as ataxia, hyperkinesis, and hallucinations.

The review discusses the significant toxicity associated with these mushrooms, highlighting the need for awareness and understanding of their pharmacology, clinical effects, and potential treatment for adverse reactions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Hallucinogenic mushrooms]. Reingardiene, D., Vilcinskaite, J., Lazauskas, R.[2018]

This study identified phenylethylamine in Psilocybe semilanceata mushrooms, which may contribute to adverse reactions during psilocybin intoxication, as evidenced by a case involving three young men who experienced severe symptoms.

The levels of phenylethylamine in these mushrooms can vary significantly, with the highest concentration found in the case of hospitalization, suggesting that this compound could play a role in the tachycardia and other symptoms not directly linked to psilocybin.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Presence of phenylethylamine in hallucinogenic Psilocybe mushroom: possible role in adverse reactions. Beck, O., Helander, A., Karlson-Stiber, C., et al.[2019]

Citations

1. en.wikipedia.org en.wikipedia.org/wiki/Psilocybin

Psilocybin Psilocybin, also known as 4-phosphoryloxy-N,N-dimethyltryptamine (4-PO-DMT), is a naturally occurring tryptamine alkaloid and investigational drug found in ...

2. pubchem.ncbi.nlm.nih.gov pubchem.ncbi.nlm.nih.gov/compound/Psilocybin

Psilocybin | C12H17N2O4P | CID 10624 - PubChem - NIH Psilocybin is a tryptamine alkaloid that is N,N-dimethyltryptamine carrying an additional phosphoryloxy substituent at position 4.

3. en.wikipedia.org en.wikipedia.org/wiki/Psilocin

Psilocin Psilocin, also known as 4-hydroxy-N,N-dimethyltryptamine (4-HO-DMT), is a substituted tryptamine alkaloid and a serotonergic psychedelic.

4. webbook.nist.gov webbook.nist.gov/cgi/cbook.cgi?ID=520-52-5

Psilocybine - the NIST WebBook Psilocybine's formula is C12H17N2O4P, molecular weight is 284.2481, CAS number is 520-52-5, and also known as Psilocybin.

5. zfin.org zfin.org/CHEBI:8614

ZFIN ChEBI: psilocybin A tryptamine alkaloid that is N,N-dimethyltryptamine carrying an additional phosphoryloxy substituent at position 4. The major hallucinogenic alkaloid isolated ...